2011 ASCO: EntreMed’s ENMD-2076 Demonstrates Clinical Activity in Recurrent, Platinum-Resistant Ovarian Cancer Patients

EntreMed, Inc. announced that ENMD-2076 demonstrated clinical activity — a six-month progression free survival rate of 19% — when administered as a single agent to platinum drug-resistant recurrent ovarian cancer patients. The announcement is based upon interim phase 2 data presented today at the 2011 American Society of Clinical Oncology Annual Meeting. 

Ursula A. Matulonis, M.D., Medical Director, Gynecologic Oncology, Dana-Farber Cancer Institute; Associate Professor of Medicine, Harvard Medical School

EntreMed, Inc., a clinical-stage pharmaceutical company developing therapeutics for the treatment of cancer announced today the presentation of clinical data for its phase 2 study with ENMD-2076 in platinum drug-resistant recurrent ovarian cancer patients. The data were presented by the principal investigator for the study, Dr. Ursula A. Matulonis, medical director of gynecologic oncology at the Dana-Farber Cancer Institute and associate professor of medicine, Harvard Medical School, during a poster discussion session at the American Society of Clinical Oncology (ASCO) Annual Meeting being held June 3 – 7, 2011 in Chicago, Illinois.

The trial was an open-label, single-arm, multicenter study of ENMD-2076 dosed orally as a single agent in patients with platinum-resistant recurrent ovarian, peritoneal or fallopian tubal cancer. The study was conducted at six sites in the United States and Canada and included the Dana-Farber Cancer Institute, Indiana University Melvin & Bren Simon Cancer Center, University of Chicago Medical Center, Memorial Sloan-Kettering Cancer Center, University of Colorado Cancer Center, and Princess Margaret Hospital. Sixty-four patients were enrolled, of which 57 were evaluable at the time of the presentation. The primary endpoint for the study was progression-free survival rate at six months. Secondary end-points include response rate, duration of response, and overall survival.

ENMD-2076 demonstrated clinical activity when administered daily orally as a single agent. Interim data from 57 evaluable patients showed a six-month progression free survival rate of 19 percent. Of the evaluable patients, four patients achieved a partial response and 30 patients achieved stable disease as measured by RECIST v1.1. Median overall survival has not yet been reached. The side effect profile was consistent with activity against ENMD-2076’s molecular targets, in particular, VEGFR2 (vascular endothelial growth factor receptor-2) and Aurora A. Studies to evaluate potential markers of ENMD-2076 in this patient group are ongoing.

Dr. Matulonis commented on the results of the study, “ENMD-2076 has demonstrated impressive anti-cancer activity in platinum-resistant ovarian cancer which is notoriously difficult to treat, and these patients have few options.”

EntreMed’s chief medical officer, Carolyn F. Sidor, M.D., M.B.A., added, “These results are very encouraging as they support further development of ENMD-2076 and also help us clarify its developmental path in ovarian cancer. We are currently designing the next clinical trial in this indication and look forward to opportunities to make ENMD-2076 available to ovarian cancer patients in the future.”

About ENMD-2076

ENMD-2076 is an orally-active, Aurora A/angiogenic kinase inhibitor with a unique kinase selectivity profile and multiple mechanisms of action. ENMD-2076 has been shown to inhibit a distinct profile of angiogenic tyrosine kinase targets in addition to the Aurora A kinase. Aurora kinases are key regulators of mitosis (cell division), and are often over-expressed in human cancers. ENMD-2076 also targets the VEGFR, Flt-3 and FGFR3 kinases which have been shown to play important roles in the pathology of several cancers. ENMD-2076 has shown promising activity in phase I clinical trials in solid tumor cancers, leukemia, and multiple myeloma. While ENMD-2076 is currently in a phase 2 trial in ovarian cancer, preclinical and clinical activities are ongoing in assessing the compound’s applicability in other forms of cancer.

To view an Adobe Reader PDF copy of the presentation, visit http://www.entremed.com/files/umatulonis_enmd_2076_p2_ovarian.pdf

About EntreMed

EntreMed, Inc. is a clinical-stage pharmaceutical company committed to developing ENMD-2076, a selective angiogenic kinase inhibitor, for the treatment of cancer. ENMD-2076 is currently in a multi-center phase 2 study in ovarian cancer and in several phase 1 studies in solid tumors, multiple myeloma, and leukemia.

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Estrogen Replacement Therapy Speeds Growth of ER+ Ovarian Cancer & Increases Risk of Lymph Node Metastasis

Estrogen therapy used by menopausal women causes “estrogen receptor positive” (ER+) ovarian cancer to grow five times faster, according to a new study being published by researchers at the University of Colorado Cancer Center in the November 1 issue of Cancer Research.

Estrogen therapy used by menopausal women causes so-called “estrogen receptor positive” (ER+) ovarian cancer to grow five times faster, according to a new study being published tomorrow by researchers at the University of Colorado Cancer Center.

Menopausal estrogen replacement therapy (ERT) also significantly increases the likelihood of the cancer metastasizing to the lymph nodes, according to the study, which will be published in the November 1 issue of Cancer Research. The study was released online on Oct. 19, 2010. Cancer Research, published by the American Association for Cancer Research, is the world’s largest (based upon circulation) medical journal devoted specifically to cancer research.

The effect of ERT was shown in mouse models of estrogen receptor positive (ER+) ovarian cancer, which accounts for about 60 percent of all human ovarian cancer cases. Ovarian cancer is one of the deadliest cancers affecting women. This year alone, nearly 22,000 women will be newly diagnosed with ovarian cancer and an estimated 13,850 women will die from the disease, according to the National Cancer Institute.

Monique Spillman, M.D., Ph.D., Gynecologic Oncologist, University of Colorado Hospital; Assistant Professor, Obstetrics & Gynecology, University of Colorado School of Medicine.

“We showed that estrogen replacement substantially increases proliferation and risk of distant lymph node metastasis in ER+ tumors,” says Monique Spillman, M.D., Ph.D., the study’s lead researcher, a gynecologic oncologist at University of Colorado Hospital and assistant professor at of obstetrics and gynecology at the University of Colorado School of Medicine.

For the first time, Spillman and her team measured ovarian cancer growth in the abdomen of mice using novel techniques for visualizing the cancer. In mice with ER+ ovarian cancer cells, which were tagged with a firefly-like fluorescent protein that allowed them to be tracked, the introduction of estrogen therapy made the tumors grow five times faster than in mice that did not receive the ERT. The risk of the cancer moving to the lymph nodes increased to 26 percent in these mice compared with 6 percent in mice that did not receive ERT.

The team also found that the estrogen-regulated genes in ovarian cancer reacted differently than ER+ genes found in breast cancer, helping to explain why current anti-estrogen therapies used with breast cancer, such as tamoxifen, are largely ineffective against ovarian cancer.

“Breast cancer and ovarian cancer are often linked when talking about hormone replacement therapy, but we found that only 10 percent of the ER+ genes overlapped,” Spillman says. “We were able to identify estrogen-regulated genes specific to ER+ ovarian cancer that are not shared with ER+ breast cancers. We believe these genes can be specifically targeted with new anti-estrogen therapies that could more effectively treat ER+ ovarian cancers.”

“Breast cancer and ovarian cancer are often linked when talking about hormone replacement therapy, but we found that only 10 percent of the ER+ genes overlapped.  We were able to identify estrogen-regulated genes specific to ER+ ovarian cancer that are not shared with ER+ breast cancers. We believe these genes can be specifically targeted with new anti-estrogen therapies that could more effectively treat ER+ ovarian cancers.”

— Monique Spillman, M.D., Ph.D., Gynecologic Oncologist, University of Colorado Hospital; Assistant Professor, Obstetrics & Gynecology, University of Colorado School of Medicine.

Spillman and her team now will begin to screen current anti-estrogen therapies against the newly identified ovarian cancer genes to identify the [biological] pathways and compounds relevant to the treatment for ER+ ovarian cancer.

This study looked at the effect of estrogen replacement therapy in mice that already possessed ER+ ovarian cancer cells. It did not test whether the estrogen replacement actually could cause the development of these cancer cells. The study also dealt only with estrogen replacement, which is linked to higher risks of ovarian cancer, not combined estrogen/progesterone therapy that is used with women who retain their uteruses.

This research is too early to draw implications for use of estrogen replacement therapy in women, Spillman cautions. “We cannot make clinical recommendations based on what is happening in mice,” says Spillman, one of just eight gynecological oncologists in Colorado. “Every woman is different and needs to talk to her doctor about the decision to use hormone replacement therapy.”

The study was funded by a Gynecologic Cancer Foundation Career Development Award and the Liz Tilberis Scholars Award from the Ovarian Cancer Research Foundation. This competitive award, a $450,000 three-year grant, is given to early-career researchers who are developing techniques for early diagnosis and improved care for women with ovarian cancer.

About the University of Colorado Cancer Center

The University of Colorado Cancer Center is the Rocky Mountain region’s only National Cancer Institute-designated comprehensive cancer center. NCI has given only 40 cancer centers this designation, deeming membership as “the best of the best.” Headquartered on the University of Colorado Denver Anschutz Medical Campus, UCCC is a consortium of three state universities (Colorado State University, University of Colorado at Boulder and University of Colorado Denver) and five institutions (The Children’s Hospital, Denver Health, Denver VA Medical Center, National Jewish Health and University of Colorado Hospital). Together, our 440+ members are working to ease the cancer burden through cancer care, research, education and prevention and control. Learn more at www.uccc.info.

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